Core–shell monodisperse spherical mSiO2/Gd2O3:Eu3+@mSiO2 particles as potential multifunctional theranostic agents

  • Daniil A. Eurov
  • Dmitry A. Kurdyukov
  • Demid A. Kirilenko
  • Julia A. Kukushkina
  • Alexei V. Nashchekin
  • Alexander N. Smirnov
  • Valery G. Golubev
Research Paper


Core–shell nanoparticles with diameters in the range 100–500 nm have been synthesized as monodisperse spherical mesoporous (pore diameter 3 nm) silica particles with size deviation of less than 4 %, filled with gadolinium and europium oxides and coated with a mesoporous silica shell. It is shown that the melt technique developed for filling with gadolinium and europium oxides provides a nearly maximum filling of mesopores in a single-run impregnation, with gadolinium and europium uniformly distributed within the particles and forming no bulk oxides on their surface. The coating with a shell does not impair the monodispersity and causes no coagulation. The coating technique enables controlled variation of the shell thickness within the range 5–100 % relative to the core diameter. The thus produced nanoparticles are easily dispersed in water, have large specific surface area (300 m2 g−1) and pore volume (0.3 cm3 g−1), and are bright solid phosphor with superior stability in aqueous media. The core–shell structured particles can be potentially used for cancer treatment as a therapeutic agent (gadolinium neutron-capture therapy and drug delivery system) and, simultaneously, as a multimodal diagnostic tool (fluorescence and magnetic resonance imaging), thereby serving as a multifunctional theranostic agent.


Core–shell nanoparticles Mesoporous silica Theranostic agent Gadolinium Europium 



The authors are grateful to E. Yu. Stovpiaga for assistance in syntheses of monodisperse mSiO2 particles, to V. V. Sokolov for measurements of the true density of the samples, to A. V. Shvidchenko for assistance in measurements of the zeta potential of the particles, and to V. Yu. Davydov and A. A. Sitnikova for fruitful discussions. This work was supported by the Russian Foundation for Basic Research (project no. 15-52-12011) and the Program no. 1 of the Presidium of the Russian Academy of Sciences. The study was in part carried out at the Joint Research Center “Material science and characterization in advanced technology”.

Supplementary material

11051_2015_2891_MOESM1_ESM.docx (204 kb)
Supplementary material 1 (DOCX 204 kb)


  1. Ambrogio MW, Thomas CR, Zhao Y-L, Zink JI, Stoddart JF (2011) Mechanized silica nanoparticles: a new frontier in theranostic nanomedicine. Acc Chem Res 44:903–913CrossRefGoogle Scholar
  2. Barreto JA, O’Malley W, Kubeil M, Graham B, Stephan H, Spiccia L (2011) Nanomaterials: applications in cancer imaging and therapy. Adv Mater 23:H18–H40CrossRefGoogle Scholar
  3. Behrens S (2011) Preparation of functional magnetic nanocomposites and hybrid materials: recent progress and future directions. Nanoscale 3:877–892CrossRefGoogle Scholar
  4. Bruckman MA, Yu X, Steinmetz NF (2013) Engineering Gd-loaded nanoparticles to enhance MRI sensitivity via T1 shortening. Nanotechnology 24:462001CrossRefGoogle Scholar
  5. Cannas C, Casu M, Mainas M, Musinu A, Piccaluga G, Polizzi S, Speghinic A, Bettinelli M (2003) Synthesis, characterisation and optical properties of nanocrystalline Y2O3–Eu3+ dispersed in a silica matrix by a deposition–precipitation method. J Mater Chem 13:3079–3084CrossRefGoogle Scholar
  6. Cheng Z, Zaki AA, Hui JZ, Muzykantov VR, Tsourkas A (2012) Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities. Science 338:903–910CrossRefGoogle Scholar
  7. Colilla M, González B, Vallet-Regí M (2013) Mesoporous silica nanoparticles for the design of smart delivery nanodevices. Biomater Sci 1:114–134CrossRefGoogle Scholar
  8. Davydov VYu, Golubev VG, Kartenko NF, Kurdyukov DA, Pevtsov AB, Sharenkova NV, Brogueira P, Schwarz R (2000) Fabrication and structural studies of opal-III nitride nanocomposites. Nanotechnology 11:291–294CrossRefGoogle Scholar
  9. de Jongh PE, Eggenhuisen TM (2013) Melt infiltration: an emerging technique for the preparation of novel functional nanostructured materials. Adv Mater 25:6672–6690CrossRefGoogle Scholar
  10. Di W, Ren X, Zhao H, Shirahata N, Sakka Y, Qin W (2011) Single-phased luminescent mesoporous nanoparticles for simultaneous cell imaging and anticancer drug delivery. Biomaterials 32:7226–7233CrossRefGoogle Scholar
  11. Feofilov SP, Kulinkin AB, Eurov DA, Kurdyukov DA, Golubev VG (2014) Fluorescence spectroscopy study of mesoporous SiO2 particles containing Gd2O3:Eu3+. Mater Res Express 1:025019CrossRefGoogle Scholar
  12. Geninatti-Crich S, Alberti D, Szabo I, Deagostino A, Toppino A, Barge A, Ballarini F, Bortolussi S, Bruschi P, Protti N, Stella S, Altieri S, Venturello P, Aime S (2011) MRI-guided neutron capture therapy by use of a dual gadolinium/boron agent targeted at tumour cells through upregulated low-density lipoprotein transporters. Chem Eur J 17:8479–8486CrossRefGoogle Scholar
  13. Grudinkin SA, Kaplan SF, Kartenko NF, Kurdyukov DA, Golubev VG (2008) Opal-hematite and opal-magnetite films: lateral infiltration, thermodynamically driven synthesis, photonic crystal properties. J Phys Chem C 112:17855–17861CrossRefGoogle Scholar
  14. Hosmane NS, Maguire JA, Zhu Y, Takagaki M (2012) Boron and gadolinium neutron capture therapy for cancer treatment. World scientific publishing company Co Pte Ltd, SingaporeCrossRefGoogle Scholar
  15. Kim TH, Lee S, Chen X (2013) Nanotheranostics for personalized medicine. Expert Rev Mol Diagn 13:257–269CrossRefGoogle Scholar
  16. Kondrashina OV (2013) A targeted drug delivery system of Gd3+ for neutron capture therapy against cancer is metalorganic magnetic nanoparticles. J Nanomed Biother Discov 3:1000116CrossRefGoogle Scholar
  17. Lammers T, Rizzo LY, Storm G, Kiessling F (2012) Personalized nanomedicine. Clin Cancer Res 18:4889–4894CrossRefGoogle Scholar
  18. Leinweber G, Barry DP, Trbovich MJ, Burke JA, Drindak NJ, Knox HD, Ballad RV, Block RC, Danon Y, Severnyak LI (2006) Neutron capture and total cross-section measurements and resonance parameters of gadolinium. Nucl Sci Eng 154:261–279CrossRefGoogle Scholar
  19. Lin Y-S, Hung Y, Su J-K, Lee R, Chang C, Lin M-L, Mou C-Y (2004) Gadolinium(III)-incorporated nanosized mesoporous silica as potential magnetic resonance imaging contrast agents. J Phys Chem B 108:15608–15611CrossRefGoogle Scholar
  20. Liu Z, Liu X, Yuan Q, Dong K, Jiang L, Li Z, Ren J, Qu X (2012) Hybrid mesoporous gadolinium oxide nanorods: a platform for multimodal imaging and enhanced insoluble anticancer drug delivery with low systemic toxicity. J Mater Chem 22:14982–14990CrossRefGoogle Scholar
  21. Minelli C, Lowe SB, Stevens MM (2010) Engineering nanocomposite materials for cancer therapy. Small 6:2336–2357CrossRefGoogle Scholar
  22. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nature Nanotech 2:751–760CrossRefGoogle Scholar
  23. Raman NK, Anderson MT, Brinker CJ (1996) Template-based approaches to the preparation of amorphous, nanoporous silicas. Chem Mater 8:1682–1701CrossRefGoogle Scholar
  24. Rosenholm JM, Sahlgren C, Lindén M (2010) Towards multifunctional, targeted drug delivery systems using mesoporous silica nanoparticles—opportunities & challenges. Nanoscale 2:1870–1883CrossRefGoogle Scholar
  25. Shi D (2009) Integrated multifunctional nanosystems for medical diagnosis and treatment. Adv Funct Mater 19:3356–3373CrossRefGoogle Scholar
  26. Slowing II, Trewyn BG, Giri S, Lin VS-Y (2007) Mesoporous silica nanoparticles for drug delivery and biosensing applications. Adv Funct Mater 17:1225–1236CrossRefGoogle Scholar
  27. Tang F, Li L, Chen D (2012) Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater 24:1504–1534CrossRefGoogle Scholar
  28. Taylor-Pashow KML, Rocca JD, Huxford RC, Lin W (2010) Hybrid nanomaterials for biomedical applications. Chem Commun 46:5832–5849CrossRefGoogle Scholar
  29. Trofimova EYu, Kurdyukov DA, Yakovlev SA, Kirilenko DA, Kukushkina YuA, Nashchekin AV, Sitnikova AA, Yagovkina MA, Golubev VG (2013) Monodisperse spherical mesoporous silica particles: fast synthesis procedure and fabrication of photonic-crystal films. Nanotechnology 24:155601CrossRefGoogle Scholar
  30. Vivero-Escoto JL, Slowing II, Trewyn BG, Lin VS-Y (2010) Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small 6:1952–1967CrossRefGoogle Scholar
  31. Wu S-H, Hung Y, Mou C-Y (2011) Mesoporous silica nanoparticles as nanocarriers. Chem Commun 47:9972–9985CrossRefGoogle Scholar
  32. Xu Z, Gao Y, Huang S, P’an Ma, Lin J, Fang J (2011a) A luminescent and mesoporous core-shell structured Gd2O3:Eu3+@nSiO2@mSiO2 nanocomposite as a drug carrier. Dalton Trans 40:4846–4854CrossRefGoogle Scholar
  33. Xu Z, Li C, P’an Ma, Hou Z, Yang D, Kang X, Lin J (2011b) Facile synthesis of an up-conversion luminescent and mesoporous Gd2O3:Er3+@nSiO2@mSiO2 nanocomposite as a drug carrier. Nanoscale 3:661–667CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Daniil A. Eurov
    • 1
  • Dmitry A. Kurdyukov
    • 1
    • 2
  • Demid A. Kirilenko
    • 1
  • Julia A. Kukushkina
    • 1
  • Alexei V. Nashchekin
    • 1
  • Alexander N. Smirnov
    • 1
  • Valery G. Golubev
    • 1
  1. 1.Ioffe Physical–Technical InstituteSt. PetersburgRussia
  2. 2.ITMO UniversitySt. PetersburgRussia

Personalised recommendations